- Spousal bereavement after dementia caregiving: A turning point for immune health Wilson, Stephanie J., Padin, Avelina C., Bailey, Brittney E., Laskowski, Bryon, Andridge, Rebecca, Malarkey, William B., and Kiecolt-Glaser, Janice K. Psychoneuroendocrinology 2020
Losing a spouse can increase the risk for premature mortality, and declines in immune health are thought to play a role. Most of the supporting data have come from cross-sectional studies comparing already-bereaved individuals to matched controls, which provides valuable information about health disparities between groups but does not reveal health changes over time. Moreover, the health consequences of bereavement may be unique for dementia family caregivers, a large and growing segment of the population. The current study sought to evaluate the course of health around 52 dementia spousal caregivers’ bereavement by capturing lymphocyte proliferation to Con A and PHA and self-rated health before and after spousal loss. To investigate the moderating role of the social environment, we examined associations between social ties and health trajectories before and after spousal loss. Using piecewise linear mixed models to allow for turning points in caregivers’ trajectories, we found that, for the average caregiver, lymphocyte proliferation to both mitogens weakened as bereavement neared and continued to decline after the loss, but at a slower pace. In tandem, perceived health degraded as bereavement approached but rebounded thereafter. Further, we found that socially isolated caregivers showed marked declines in immune responses to Con A and PHA over time both before and after bereavement, whereas their socially connected counterparts had shallower declines to PHA and maintained a level immune response to Con A. In addition, socially isolated caregivers reported poorer health before and after bereavement compared to their counterparts, whose self-rated health declined as the loss neared but later recovered to exceed prior levels. These findings shed new light on the dynamics of immune function in response to spousal bereavement after dementia caregiving: longitudinal data reveal a pattern of health recovery following caregivers’ loss, particularly among those with more robust social networks prior to bereavement
- Multiple imputation by predictive mean matching in cluster-randomized trials Bailey, Brittney E., Andridge, Rebecca, and Shoben, Abigail B. BMC Medical Research Methodology 2020
Background: Random effects regression imputation has been recommended for multiple imputation (MI) in cluster randomized trials (CRTs) because it is congenial to analyses that use random effects regression. This method relies heavily on model assumptions and may not be robust to misspecification of the imputation model. MI by predictive mean matching (PMM) is a semiparametric alternative, but current software for multilevel data relies on imputation models that ignore clustering or use fixed effects for clusters. When used directly for imputation, these two models result in underestimation (ignoring clustering) or overestimation (fixed effects for clusters) of variance estimates. Methods: We develop MI procedures based on PMM that leverage these opposing estimated biases in the variance estimates in one of three ways: weighting the distance metric (PMM-dist), weighting the average of the final imputed values from two PMM procedures (PMM-avg), or performing a weighted draw from the final imputed values from the two PMM procedures (PMM-draw). We use Monte-Carlo simulations to evaluate our newly proposed methods relative to established MI procedures, focusing on estimation of treatment group means and their variances after MI. Results: The proposed PMM procedures reduce the bias in the MI variance estimator relative to established methods when the imputation model is correctly specified, and are generally more robust to model misspecification than even the random effects imputation methods. Conclusions: The PMM-draw procedure in particular is a promising method for multiply imputing missing data from CRTs that can be readily implemented in existing statistical software.
- Cognitive problems of breast cancer survivors on proton pump inhibitors Madison, Annelise A., Woody, Alex, Bailey, Brittney, Lustberg, Maryam B., Ramaswamy, Bhuvaneswari, Wesolowski, Robert, Williams, Nicole, Reinbolt, Raquel, VanDeusen, Jeffrey B., Sardesai, Sagar, Malarkey, William B., and Kiecolt-Glaser, Janice K. Journal of Cancer Survivorship 2020
Purpose: Proton pump inhibitors (PPIs) are used in cancer patients to manage treatment-related gastrointestinal symptoms and to prevent damage to the gastric mucosal lining during treatment. However, PPI use may contribute to cognitive problems. To compare PPI-users and non-users, breast cancer survivors reported cognitive problems in three studies. Methods: In Study 1, breast cancer survivors (N = 209; n = 173 non-users, n = 36 PPI-users; stages 0-IIIC) rated their cognitive function on the Kohli scale prior to cancer treatment, as well as one and two years later. In Study 2, women (N = 200; n = 169 non-users, n = 31 PPI-users, stages 0-IIIa, M = 11 months post-treatment) rated their cognitive function on the Kohli scale and BCPT checklist at three visits over a six-month period. In Study 3, participants (N = 142; n = 121 non-users, n = 21 PPI-users; stages I-IIIa, M = 4 years post-treatment) rated their cognitive function on the Kohli scale, BCPT checklist, and Functional Assessment of Cancer Therapy cognitive scale (FACT-cog). Results: In Study 1, PPI-users reported more severe concentration problems (p = 0.039) but not memory problems (p = 0.17) than non-users. In Study 2, PPI-users reported more severe concentration problems (p = 0.022) than non-users, but not memory problems or symptoms on the BCPT (ps = 0.11). Study 3’s PPI-users reported more severe memory problems (p = 0.002), poorer overall cognitive function (p = 0.006), lower quality of life related to cognitive problems (p = 0.005), greater perceived cognitive impairment (p = 0.013), and poorer cognitive abilities (p = 0.046), but not more severe concentration problems (p = 0.16), compared to non-users. Conclusions/implications: PPI use may impair breast cancer survivors’ memory, concentration, and quality of life.
- Linking marital support to aging-related biomarkers: Both age and marital quality matter Wilson, Stephanie J., Bailey, Brittney E., Malarkey, William B., and Kiecolt-Glaser, Janice K. The Journals of Gerontology: Series B 2019
Objectives Marital support is central to couples’ relationships, yet support’s health implications can vary widely. Guided by attribution bias and aging theories, the current study examined whether age and marital satisfaction moderate the links of perceived and received spousal support to aging-related biomarkers. Methods Couples (N = 93, ages 22–77) rated marital satisfaction, overall perceived spousal support, and the quality of support received from their spouse in a lab- based discussion. Blood samples collected at baseline, immediately post- discussion, 3 hr post-discussion, and end-of-visit were assayed for proinflammatory cytokines tumor necrosis factor (TNF)-αand interleukin (IL)-6, as well as insulin-like growth factor (IGF)-1. Results Consistent with predictions, less satisfied older couples who received lower- quality spousal support during their discussion had greater increases in TNF-αthan those who received higher-quality support; highly satisfied couples of all ages and less satisfied younger couples did not show these inflammatory changes. Highly satisfied older couples with greater perceived spousal support had lower TNF-αacross the day and higher IGF-1. Discussion Marital satisfaction and age may shape spousal support’s significance for healthy aging. Rose-colored lenses worn only in the most satisfying marriages may protect couples from the possible health risks of low-quality received support and enhance potential benefits of perceived support. For better or worse, these health implications may grow with older age.
- Physical activity after breast cancer surgery: Does depression make exercise feel more effortful than it actually is? Padin, Avelina C., Wilson, Stephanie J., Bailey, Brittney E., Malarkey, William B., Lustberg, Maryam B., Farrar, William B., Povoski, Stephen P., Agnese, Doreen M., Reinbolt, Raquel E., Wesolowski, Robert, Williams, Nicole, Sardesai, Sagar, Ramaswamy, Bhuvaneswari, Noonan, Anne M., Vandeusen, Jeffrey B., Haas, Garrie J., and Kiecolt-Glaser, Janice K. International Journal of Behavioral Medicine 2019
Background: Prior to treatment, breast cancer patients are less physically fit compared to peers; during cancer treatment, their fitness typically declines. Depressive symptoms are associated with reduced activity up to 5 years post-treatment, but research has not identified mechanisms linking depression and lower activity. The current study assessed relationships among breast cancer patients’ depression and perceived exertion during exercise as well as heart rate, an objective indicator of exertion. Methods: Participants were 106 breast cancer patients, stages I–IIIA, who completed surgery but had not started adjuvant treatment. Heart rate and self-rated exertion, measured using the Borg Scale of Perceived Exertion, were assessed every 2 min during a graded exercise test. Depression was assessed using the CES-D and a structured clinical interview. Results: Compared to women below the CES-D clinical cutoff, women with significant depressive symptoms reported steeper increases in exertion during the exercise test (p =.010) but had similar heart rates (p =.224) compared to women below the cutoff. Major depression history was unrelated to perceived exertion (ps \textgreater.224) and heart rate (ps \textgreater.200) during exercise. Conclusions: Women with currently elevated depressive symptoms experienced exercise as more difficult compared to women below the CES-D cutoff, but these self-perceptions did not reflect actual heart rate differences. Depression may make exercise feel more demanding, which could ultimately decrease patients’ likelihood of engaging in regular exercise. Results support the use of depression screening tools following breast cancer surgery to identify and intervene on individuals at risk for decreased physical activity during survivorship.
- When couples’ hearts beat together: Synchrony in heart rate variability during conflict predicts heightened inflammation throughout the day Wilson, Stephanie J., Bailey, Brittney E., Jaremka, Lisa M., Fagundes, Christopher P., Andridge, Rebecca, Malarkey, William B., Gates, Kathleen M., and Kiecolt-Glaser, Janice K. Psychoneuroendocrinology 2018
Hostile conflict in marriage can increase risks for disease and mortality. Physiological synchrony between partners—e.g., the linkage between their autonomic fluctuations—appears to capture engagement, or an inability to disengage from an exchange, and thus may amplify the health risks of noxious interactions such as marital conflict. Prior work has not examined the unique health correlates of this physiological signature. To test associations between couples’ heart rate variability (HRV) synchrony during conflict and inflammation, 43 married couples engaged in a marital problem discussion while wearing heart monitors and provided four blood samples; they repeated this protocol at a second visit. When couples’ moment-to-moment HRV changes tracked more closely together during conflict, they had higher levels of three inflammatory markers (i.e., IL-6, stimulated TNF-α, and sVCAM-1) across the day. Stronger HRV synchrony during conflict also predicted greater negative affect reactivity. Synchrony varied within couples, and was related to situational factors rather than global relationship traits. These data highlight partners’ HRV linkage during conflict as a novel social-biological pathway to inflammation-related disease.
- Thoughts after marital conflict and punch biopsy wounds: Age-graded pathways to healing Wilson, Stephanie J., Andridge, Rebecca, Peng, Juan, Bailey, Brittney E., Malarkey, William B., and Kiecolt-Glaser, Janice K. Psychoneuroendocrinology 2017
Thoughts and emotions following marital conflict have received little attention but almost certainly contribute to marriage’s long-term health effects. Consistent with emotion theories of aging, we expected the effects of post-conflict thoughts on important neuroendocrine and immune outcomes, cortisol levels and full-thickness wound healing, to differ by age. An age-diverse sample of married couples received a punch biopsy wound and discussed a marital problem, then privately recorded their thoughts and rated their mood. Salivary cortisol was sampled throughout the day, and wound healing was measured for 32 days. Older adults reported more positive mood post-conflict than younger adults. Thoughts with more positive emotional content related to lower subsequent cortisol levels. Only older adults who expressed more positive thoughts after conflict experienced faster wound healing, not younger adults. These findings point to the increased physiological importance of regulatory post-stressor processes in older age, and broaden our understanding of social-emotional age differences in close relationships. These data also stimulate questions of whether marriage has more widespread health consequences for older partners, undetected in studies of short-term outcomes.
- Erythrocyte linoleic acid, but not oleic acid, is associated with improvements in body composition in men and women Belury, Martha A., Cole, Rachel M., Bailey, Brittney E., Ke, Jia-Yu, Andridge, Rebecca R., and Kiecolt-Glaser, Janice K. Molecular Nutrition and Food Research 2016
SCOPE: Supplementation with linoleic acid (LA; 18:2Omega6)-rich oils increases lean mass and decreases trunk adipose mass in people. Erythrocyte fatty acids reflect the dietary pattern of fatty acid intake and endogenous metabolism of fatty acids. The aim of this study is to determine the relationship of erythrocyte LA, with aspects of body composition, insulin resistance and inflammation. Additionally, we tested for relationships of oleic acid (OA) and the sum of long chain omega-three fatty acids (LC-Omega3-SUM), on the same outcomes. METHODS AND RESULTS: Men and women (N = 139) were evaluated for body composition, insulin resistance, and serum inflammatory markers, interleukin-6 (IL-6) and c-reactive protein (CRP) and erythrocyte fatty acid composition after an overnight fast. LA was positively related to appendicular lean mass/body mass index (ALM/BMI) and inversely related to trunk adipose mass. Additionally, LA was inversely related to insulin resistance and IL-6. While there was an inverse relationship between OA or LC-Omega3-SUM with markers of inflammation, there were no relationships between OA or LC-Omega3-SUM with body composition or HOMA-IR. CONCLUSIONS: Higher erythrocyte LA was associated with improved body composition, insulin resistance and inflammation. Erythrocyte OA or LC-Omega3-SUM was unrelated to body composition and insulin resistance. There is much controversy about whether all unsaturated fats have the same benefits for metabolic syndrome and weight gain. We sought to test the strength of the relationships between three unsaturated fatty acid in erythrocytes with measurements of body composition, metabolism, and inflammation in healthy adults. Linoleic acid, but not oleic acid or the sum of long chain omega 3 fatty acids (w3), was associated with increased appendicular lean mass and decreased trunk adipose mass and insulin resistance. This article is protected by copyright. All rights reserved.